Gamma nitro-gamma, gamma dicarbalkoxy-butyraldehydes and process



Patented Apr. 3, 1951 :2 5.1-;

GAMMA NITRO-GAMMAGAMMA DICAR- BALKOXY' BUTYRALDEHYDES AND PROCESS Owen A. Moe and Donald T. Warner, Minneapolis Minn., assignors to General Mills, Inc., a corporationeof Delaware No Drawing. Application February 24, 1948, Serial No. 10,557

8 Claims. (01. 260-483) The present invention relates to the preparation of various'nitroaldehydes which are particularly useful for the synthesis of various amino acids and which are also useful for other syntheses. I I

The aldehydo compounds contemplated by the present invention may be illustrated by the following formula:

COOR

OaNCCOOR HR in which R, R R and R, represent hydrogen or low aliphatic groups such as methyl, ethyl, propyl, butyl, and the like, and may be alike or different. The aldehydes in which R and R are hydrogen are useful in the preparation of tryptophane, lysine, ornith'rne, proline, and numerous other compounds. The aldehydes in which R or R are alkyl are suitable for the synthesis of alkyl-substituted amino acids, as well as other compounds.

It is, therefore, an object of the present invention to provide novel aldehydo compounds which are particularly useful for the synthesis of amino acids.

It is another object ofmthe present invention to provide a novel process of producing these compounds.

These and other objects of'the invention will be more fully apparent from the following description, with particular reference to specific examples which are to be understood as illustrative only and not as limiting the invention.

These aldehydo compounds may be prepared by the 1,4 addition of alpha,beta-unsaturated aldehydes to nitromalonic esters in accordance with the following reaction:

HCOORI earthen-mono omtooow N0, cum (IJHRK ino wherein R, R, R and R are as above" defined.-

Typical of this type of reaction is the, addition of nitromalonic ester to acrolein. Ethyl nitromalonate may be readily prepared according to the same procedure given in the literature for the preparation of methyl nitromalonate by Arndt and Rose, J. Chem. Soc., 1 (1935).' The reaction of the nitromalonate and acrolein involves the admixing of these reactants in the presence of a basic catalyst and preferably in the presence of a solvent. Suitable catalysts include alkali metal alkoxides such as sodium ethoxide,

and tertiary low aliphatic amines such as tributyl' amine, triethyl amine, tripropyl amine, and the like. Suitable solvents include absolute ethanol and benzene. The reaction proceeds smoothly to a high yield of the desired aldehyde compound. The following examples will serve to illustrate the invention.

EXAMPLE 1 Ten grams of ethyl nitromalonate were dissolved in cc. of absolute ethanol. Three cc. of'a'crolein were added at once and no rise in the reaction temperature was noted. Twenty mg. of sodium metal were added, and the temperature increased from 24 to 28 C. An additional quantity (20 mg.) of metallic sodium was added and the temperature increased to 36 C. After stirring for approximately 30 minutes, another small portion (approximately 10 mg.) of metallic,

sodium was added. After stirring for one hour at room temperature, the reaction mixture was treated with glacial acetic acid (0.15 gm.), to yield a solution of gamma nitro,gamma-gamma dicarbethoxy butyraldehyde. Removal of solvent from a portion of this solution. by distilla-' tion yielded a residual oil which was the aldehyde compound.

Nine grams of 2,4-dinitrophenylhydrazine were mixed with 500 cc'. of ethanol, and after heating to-the boiling point the remainder of the alcoholic solution of the aldehydo compound was added. At the reflux temperature of the resulting reaction mixture, 10 cc. of concentrated hydrochloric acid were added and the reaction mixture was-boiled for an additional 2 minutes. The reaction mixture was filtered and the filtrate was permitted to cool slowly. The formation of. platelet-type crystals was noted. The precipitated 2,4-dinitrophenylhydrazone was collected by filtration and dried. The product thus obtained Tryptophane weighed 11 g. and melted at 70-73 C. The filtrate COOEt 0001 was diluted with water and an additional quantity 1 of product (4 g.) was collected. This melted at oNcooEt COHNHNH, f 60-64 C. Further dilution With water yielded 5 OH: OH: an additional quantity (2.7 g.) of material which began to melt at approximately 50 C. The entire quantity (17.7 g.) of material collected was re- Ho H NNH crystallized from ethanol. Thirteen grams of the l 2 23 or 2,4-dinitrophenylhydrazone were obtained, meltg I 7 H2504 ing at 73-75 C. Further purification by re- 3 000m crystallization from ethanol increased the melting point to 75-77 0. Analysis calc. for CisHieOioNst w ofiooom c, 43.54; H, 4.31. Found: 0, 43.71 H, 4.39. -oo,m

EXAMPLE 2 I Ten grams of ethyl nitromalonate were dis-' l solved in 60 cc. of absolute ethanol, three cc. of acrolein were added with stirring and the re- CHIfimCOOEt H2O CHKIIHCOOH action temperature did not increase. Two cc. of I NH: v i NHz tributyl amine were added in 1 cc. portions and N the reaction temperature increased to 36 C. 11 H The reaction mixture was cooled and permitted Lysine to stand overnight. Removal of the solvent by (100m 000E, distillation from a portion of the reaction mixture yielded a residual oil which was gamma nitro, GENO C O 32 0 0 0m gamma, gamma dicarbethoxy butyraldehyde. H1 CH2 A ten cc. portion of the above reaction mixture ,H, was mixed with 0.5 g. of 2,4-dinitrophenyl- J V hydrazine in 50 cc. of absolute ethanol. The ref sulting reaction mixture was heated to the reflux ON temperature. Then 1.5 cc. of concentrated hydro- 3 chloric acid was added. The resulting clear, light l yellow solution was filtered and the filtrate 000E. s COOEt yielded an oil which rapidly solidified. The solid product was collected by filtration and dried. It HMIJCOOM OiNCOOOEt started to melt at about C. and appeared to CH1 .H: be quite completely melted at 70 C. Purification Ha H by recrystallization from ethanol yielded the de- 40 5 i1 sired 2,4-dinitrophenylhydrazone melting at H 75-77 C. 7 (EH: on

Ten grams of ethyl nitromalonate were dis- 1. t if solved in cc. of benzene. .The additionof. 3 D +619 J cc. of acrolein showed no increase in the reaction COOH" temperature. The addition of 2 cc. of tributyl F .HNHI amine increased the reaction temperature quite V 1 H} rapidly to 37 C. After stirring for 2 hours at room temperature, a l0 cc.. portion of this re- 1 2 action mixture was treated with 2,4-dinitrophenylhydrazine in the usual manner. The resuiting 2,4-dinitrophenylhydrazone separated as NH: small platelets and melted at 73-75 C. Refi crystallization increased the melting point to 75-76 C. No depression in the melting point 000m CODE-F11 was observed when mixed with the previous OzNCCOOEt omcoont samples. Vacuum evaporation of a further por- 1 60. CH1 H2 tion of the original reaction mlxture yielded the desired aldehyde asaresidual oil. i While these examples have been with reference 1' to ethyl nitromalonate, other low aliphatic esters I 7 v v f 1 1 or nitromalonic acid :may be used, such as methyl, v j l s propyl, butyl, and other esters. Likewise in place COOH 1 of acrolein, methacrolein may be used to produce I l aldehydes which R is methyl. Crotonaldehyde CHNH H2O HZNCC is useful in-this reaction to produce compounds H2 C 0 7 H1 inwhich R is methyl. i,

These aldehydes are useful in numerous syn- 1 1 E theses. For purpose of illustration, the syntheses a 7 NH; NE:

of tryptophane, lysine, ornithine, and proline from gamma-nitro-gamma, gamma-clicarbethoxy where T is oxime, aldimine, phenylhydrazone, or butyraldehyde are illustrated as follows: 1 15; semicarbazone. 1.

Praline COOEt COOEt OaN COOEt H2 HzN COOEt CH H1 H0 JIHO COOEt COOEt EtOOC NH EtOOC -N CH: CH Hz-C: Hg-Cfiz H CO1 COOH H -NH CH: Hr-CHw While various modifications of the invention have been described, it is to be understood that this invention is not limited thereto, but other modifications may be made without departing from the spirit of the invention.

We claim as our invention:

1. Aldehyde compounds having the following formula:

COOR

ozNoc-oon +1111 CHRI in which R and R are low alkyl groups containing from one to four carbon atoms, and R and R are selected from the group consisting of hydrogen and methyl.

2. Process of producing gamma-nitro-gamma,

gamma-dicarbethoxy butyraldehyde which comprises reacting ethyl nitromalonate with acrolein in the presence of a small amount of alkaline catalyst.

3. Gamma-nitro, gamma-gamma dicarbethoxy butyraldehyde.

4. Alpha methyl gamma nitro gamma, gamma-dicarbethoxy butyraldehyde.

5. Beta-methyl-gamma-nitro-gamma,gammadicarbethoxy butyraldehyde.

6. Process of producing aldehydo compounds having the formula COOR o 0 0R1 (5BR $1112:

CHO

which comprises reacting the compound OaNC in which R. and R1 are alkyl groups containing from one to four carbon atoms, with an aldehyde having the formula CHR =CHR CHO No references cited. 

1. ALDEHYDO COMPOUNDS HAVING THE FOLLOWING FORMULA: 